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Review
. 2025 Mar 10;17(3):e80321.
doi: 10.7759/cureus.80321. eCollection 2025 Mar.

Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review

Jay P Patel  1 , Daksh Hardaswani  2 , Jaykumar Patel  3 , Faizanali Saiyed  4 , Rushita J Goswami  5 , Taskin I Saiyed  6 , Harshkumar Patel  7 , Trishul H Amin  8
Affiliations
Review

Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review

Jay P Patel et al. Cureus. .

Abstract

Obesity, a multifaceted and chronic condition characterized by excessive fat accumulation, poses significant risks to overall health and is associated with various metabolic and cardiovascular complications. This literature review evaluates and compares the effectiveness of four pharmacological agents semaglutide, liraglutide, orlistat, phentermine, and emerging agents like setmelanotide, amycretin, retatrutide, cagrilintide, and cotadutide in managing weight loss among obese. A detailed analysis was conducted on their mechanisms of action, dosing regimens, efficacy in weight loss, safety profiles, and their impact on obesity-related comorbidities. Although all agents presented distinct benefits, side effects such as gastrointestinal discomfort with orlistat and GLP-1 receptor agonists, and potential dependency with phentermine, necessitate tailored treatment approaches. This review highlights the importance of integrating pharmacotherapy with lifestyle interventions to achieve sustainable weight management and identifies areas for future research to optimize therapeutic outcomes for individuals with obesity.

Keywords: comparative study; liraglutide or saxenda; medical weight loss; obesity; orlistat; phentermine; phentermine-topiramate; semaglutide; weight loss; weight-loss intervention.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. The study selection process is provided following the PRISMA flowchart.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Figure 2
Figure 2. A flowchart of factors contributing to obesity.
The flow chart highlights the interplay of genetic predisposition, environmental influences, behavioral patterns, hormonal imbalances, and metabolic dysfunctions, all of which interact to disrupt energy balance and promote excessive fat accumulation. The image is created by the author (Jay P Patel) of this study.
Figure 3
Figure 3. A flowchart of semaglutide's mechanism of action.
The image is created by the author (Jay P Patel) of this study.
See this image and copyright information in PMC

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